Cisplatin dose adjustment in patients with renal impairment, which recommendations should we follow?
Cisplatin dose adjustment in patients with renal impairment, which recommendations should we follow?
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DOI：
10.1007/s11096-013-9912-7
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发表时间：
2014-04-01
影响因子：
2.4
通讯作者：
Pourroy, Bertrand
中科院分区：
文献类型：
--
作者：
Bennis, Youssef;Savry, Amandine;Pourroy, Bertrand
研究背景肾毒性是顺铂的剂量限制性副作用，需要评估肾功能以进行剂量调整。目的探讨肾功能损害患者是否采用Cockcroft-Gault(CG)公式或简化的肾脏疾病饮食调整公式(AMDRD)估算肾小球滤过率(GFR)。研究背景是在一家拥有1000张床位的大学医院进行的。方法对两年顺铂处方与4和3范围估计肾小球滤过率(EGFR)分层给药建议(分别为4RR和3RR)进行回顾性比较。主要观察指标顺铂剂量，单位为mg/m(2)，以肾功能为基础，按剂量推荐给药。结果顺铂1364个周期中，EGFR+60mL/min的患者共156例(11.4%)，中位年龄67.4岁。在这些周期中，有57个(36%)的剂量没有减少。减少剂量后，处方剂量与使用CG的4RR的推荐剂量没有差异(63+/-A12比+/-A17)，而使用aMDRD的处方剂量显著降低(66+/-A12比81+/-A22，p；0.01)，而根据CG和aMDRD的3RR显著增加(分别为63+/-A12比50+/-A3和66+/-A12比50.7+/-A4.0，p<；0.01)。根据4RR和使用aMDRD处方至少一个合适的剂量与统计学上显著更高的中位总累积剂量(分别为方案的89.9%和75.1%，p<；0.01)相关，而EGFR随时间的推移没有更高的下降。结论肾损害患者应加强顺铂剂量调整。用aMDRD公式估算GFR，并为EGFR患者增加50至59.9毫升/分钟的中等剂量减量，可能会导致顺铂的累积剂量更高，而不会产生更高的肾脏毒性，这可能会显著影响化疗的有效性。仍然需要进行前瞻性评估，以评估这一剂量适应时间表的效益/风险比，同时考虑到GFR估计的可变性。
Background Nephrotoxicity is the dose-limiting side effect of cisplatin justifying the assessment of renal function for dose adjustment. Objective To determine whether appropriate dose adjustment is made in patients with renal impairment using the Cockcroft-Gault (CG) or the abbreviated Modification of Diet in Renal Disease (aMDRD) formulas to estimate the glomerular filtration rate (GFR). Setting The study was conducted in a 1,000-bed university hospital. Method Two years of cisplatin prescriptions were retrospectively compared to the 4 and 3 ranges estimated glomerular filtration rate (eGFR)-stratified dosing recommendations (4RR and 3RR respectively). Main outcome measure Cisplatin dose in mg/m(2) based on kidney function and according to the dosing recommendations. Results Among 1,364 cycles of cisplatin, 156 (11.4 %) were prescribed for 70 patients with eGFR < 60 mL/min and a median age of 67.4 years. For 57 (36 %) of these cycles, doses were not reduced. When reduced, prescribed doses were not different than recommended doses according to 4RR using CG (% of protocol, 63 +/- A 12 vs. 64 +/- A 17) while it was significantly lower using aMDRD (% of protocol, 66 +/- A 12 vs. 81 +/- A 22, p < 0.01) and significantly higher according to 3RR using both CG and aMDRD (% of protocol, 63 +/- A 12 vs. 50 +/- A 3 and 66 +/- A 12 vs. 50.7 +/- A 4.0 respectively, p < 0.01). Prescription of at least one appropriate dose according to 4RR and using aMDRD was associated with a statistically significant higher median total cumulative dose (% of protocol, 89.9 vs. 75.1 % respectively, p < 0.01) without higher decrease of eGFR over time. Conclusion Cisplatin dose adjustment in patients with renal impairment must be improved. Estimating GFR with the aMDRD formula and adding an intermediary level of dose reduction for patients with eGFR from 50 to 59.9 mL/min may result in a higher cumulative dose of cisplatin without higher renal toxicity, which may significantly impact on the effectiveness of the chemotherapy. A prospective evaluation remains needed to assess the benefit/risk ratio of this dose adaptation schedule, taking into account the variability of the GFR estimates.